title: Design, synthesis, and biological evaluation of bifunctional thyrointegrin inhibitors: new anti-angiogenesis analogs.
abstract: BACKGROUND
  Inhibition of pathological angiogenesis.
  
  
  OBJECTIVE
  Obtaining new transactivator, bifunctional, thyroid antagonist, non-toxic anti-angiogenic compounds.
  
  
  METHODS
  In silico drug design, synthesis in bulk and biological evaluation in chick chorioallantoic membrane (CAM) model.
  
  
  RESULTS
  Significant inhibition (range 65-73%) at 0.25-2.0 μg/ml doses.
  
  
  CONCLUSIONS
  The synthesis of compounds (9), (10), and (11) incorporating long-chain moieties guanidine, urea, methyl amine and, propyl amine substitutions, respectively, into the core molecular framework of tetrac (tetraiodothyroacetic acid) were undertaken. The evaluation of the anti-angiogenic bioactivity of these compounds in the CAM model revealed no loss of activity in comparison with tetrac and XT199, which showed nearly 86% inhibition at dose levels of 1 and 0.5 μg/ml, respectively, and validated the concept.
authors.affiliation: Pharmaceutical Research Institute, Rensselaer, NY 12144, USA.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bridoux
authors.forename: Riaz A
authors.initials: RA
authors.lastname: Khan
authors.forename: Celei
authors.initials: C
authors.lastname: Chen
authors.forename: Gwenaël
authors.initials: G
authors.lastname: Chevé
authors.forename: Huadong
authors.initials: H
authors.lastname: Cui
authors.forename: Evgeny
authors.initials: E
authors.lastname: Dyskin
authors.forename: Aziz
authors.initials: A
authors.lastname: Yasri
authors.forename: Shaker A
authors.initials: SA
authors.lastname: Mousa
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004531:Eggs; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D015394:Molecular Structure; D013961:Thyroid Gland / Q000187:drug effects*
chemical_list: D020533:Angiogenesis Inhibitors; D039302:Integrin alphaVbeta3